Masticatory performance-related factors in preschool children: establishing a method to assess masticatory performance in preschool children using colour-changeable chewing gum.

A knowledge gap regarding masticatory performance in preschool children exists, which in turn delays intervention for preventive care; therefore, a method to easily assess performance is needed. The purpose of this study is to investigate the feasibility of assessing masticatory performance using colour-changeable chewing gum and to investigate masticatory performance-related factors in preschool children. This cross-sectional survey was conducted in two childcare facilities and our laboratory. First, a one-third quantity of colour-changeable chewing gum was masticated by six adults to assess the nature and progression of colour changes in this quantity. Then, masticatory performance in 370 children 4-6 years of age was assessed using the same quantity of colour-changeable chewing gum (60 chew strokes). The maximum bite force, body height, weight, age and number of healthy teeth were recorded. A t-test was performed to determine whether gum-chewing experience or lack thereof produced a significant difference in masticatory performance. The Spearman's rank correlation coefficient was then determined for masticatory performance assessment values and other factors solely for children with gum-chewing experience. Measurements from 259 children were obtained. Children with gum-chewing experience demons trated significantly higher assessment values and were deemed to have been correctly assessed. A very weak but significant positive correlation was observed only between masticatory performance and the number of healthy teeth. The masticatory performance of preschool children was easily assessed using colour-changeable chewing gum. The assessment values demonstrated significant correlation with the number of healthy teeth, but not with maximum bite force, body height, weight or age.

Fhit expression in human gastric adenomas and intramucosal carcinomas: correlation with Mlh1 expression and gastric phenotype.

The fragile histidine triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in a variety of tumours, including gastric carcinomas. Recently, it has been reported that the FHIT gene may be a target of damage in some of mismatch-deficient tumours. To clarify further the role of the Fhit protein in gastric carcinogenesis, we investigated whether Fhit expression in early gastric neoplasia is associated with mismatch repair protein expression and cellular phenotype. Fhit, Mlh1 and phenotypic expression were evaluated immunohistochemically in 87 early gastric neoplasias, comprising 32 adenomas and 55 intramucosal carcinomas, resected by endoscopic mucosal resection therapy. Significant loss or reduction of Fhit expression was noted in four (12.5%) of the 32 adenomas and 21 (38.2%) of the 55 intramucosal carcinomas. The rate of abnormal Fhit expression was significantly higher in intramucosal carcinomas than in adenomas (P=0.021). Moreover, reduced Fhit expression was found to be significantly associated with loss of Mlh1 expression in early gastric neoplasia (P=0.0011). Furthermore, we also detected a significant association between reduced Fhit expression and gastric phenotype (P=0.0018). These results suggested that reduced Fhit expression occurs in the early stage of gastric carcinogenesis and could be correlated with a lack of Mlh1 expression and gastric phenotype.

Antioxidant activity and hypoglycemic effect of ferulic acid in STZ-induced diabetic mice and KK-Ay mice.

Antioxidant activity and biological properties of ferulic acid (FA) are well recognized. This study was designed to estimate the potential utility of FA administered orally at low dosage for improvement of hyperglycemia in diabetes. With this aim we have evaluated the hypoglycemic effect of FA in two type diabetic animal models: (1) streptozotocin (STZ)-induced diabetic mice, a model of insulin-dependent diabetes mellitus (IDDM); (2) KK-Ay mice, a model of non-insulin dependent diabetes mellitus (NIDDM). In addition, we measured the production of thiobarbituric acid-reactive substances (TBARS) in brown adipose tissues of diabetic mice at the end of FA feeding experiment. FA at 0.01% and 0.1% of basal diet showed to suppress significantly blood glucose levels in STZ-induced diabetic mice. In KK-Ay mice 0.05% FA suppressed effectively blood glucose levels. In addition, FA inhibited the lipid peroxidation in brown adipose tissue of diabetic mice. Taken together, these findings suggest that dietary FA may be useful in alleviating oxidative stress and attenuating the hyperglycemic response associated with diabetes.

Reduced Fhit expression is associated with mismatch repair deficiency in human advanced colorectal carcinoma.

The Fragile Histidine Triad gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumour suppressor gene involved in multiple tumour types including colorectal carcinomas. Recently, it has been reported that the Fragile Histidine Triad gene may be a target of damage in a fraction of mismatch deficient tumours. To explore this hypothesis, we analysed both Fragile histidine triad and mismatch repair protein (Msh2 and Mlh1) expression using immumohistochemical methods in 52 advanced colorectal carcinomas (19 well-, 17 moderately-, and 16 poorly-differentiated). In addition, we examined whether the Fragile histidine triad and mismatch repair protein expression correlated with p53 expression and clinicopathological findings. Significant loss or reduction of Fragile histidine triad expression was noted in 18 of the 52 (34.6%) advanced colorectal carcinomas: 2 (10.5%) well-differentiated, 3 (17.6%) moderately-differentiated, 13 (81.3%) poorly-differentiated carcinomas, the frequency being significantly higher in the latter than that in the former two (P<0.0001). Loss of mismatch repair protein (mainly, Mlh1) expression was detected in 21 of the 52 (40.4%) colorectal carcinomas. Moreover, reduced Fragile histidine triad expression was significantly associated with absence of mismatch repair protein expression in the advanced colorectal carcinomas (P<0.0001). However, the Fragile histidine triad and mismatch repair protein expression was not significantly associated with p53 expression. These results suggested that reduced Fragile histidine triad expression might be correlated with mismatch repair expression, but not with p53 expression.

Molecular changes in the early stage of colon carcinogenesis in rats treated with azoxymethane.

To elucidate early molecular events related to colon carcinogenesis, we examined alterations in the expression of colon cancer-related genes such as cyclooxygenase (COX)-2, APC and c-Myc, cell proliferation and apoptosis in the background colon mucosa, and K-ras mutation at aberrant crypt foci (ACF) in the colons of azoxymethane (AOM)-treated rats 4 weeks after the first exposure to AOM. About 40 ACF/colon were induced in the colons of rats treated with AOM (Group 1); however, rats not treated with AOM (Group 2) showed no ACF formation in the colon. The level of AgNORs in the colonic mucosa was significantly higher in Group 1 than in Group 2 (P<0.01). The colonic mucosa in Group 1 looked macroscopically and histologically normal, but the proliferative activity of the mucosa of rats treated with AOM was clearly elevated. COX-2 mRNA expression was not detected in normal colonic mucosa in Group 2, but 3 out of 10 rats in Group 1 showed COX-2 mRNA expression in their colons by reverse transcription (RT)-polymerase chain reaction (PCR). There was a tendency toward an increased expression level of COX-2 in the AOM-treated group. The level of APC mRNA expression in Group 1 was significantly lower than that in Group 2 (P<0.01). Moreover, the level of c-Myc mRNA expression in Group 1 was significantly higher than that in Group 2 (P<0.01). An average of 0.034+/-0.006% apoptosis in colonic mucosa was detected in Group 1; the incidence of apoptosis in Group 2 was 0.021+/-0.005%. The difference between Groups 1 and 2 was significant (P<0.01). These results indicate that apoptosis was possibly induced to eliminate cells damaged by AOM administration. Six out of 22 (27%) ACF with 4 or more crypts showed K-ras mutations at codon 12; all mutations were G to A transitions (GGT to GAT). ACF with 1-3 crypts showed no mutations in the K-ras gene. In conclusion, AOM caused an increase in COX-2 and c-Myc mRNA expression, a decrease in APC mRNA expression, induction of apoptosis in normal-appearing colonic mucosa, and a K-ras mutation in ACF with 4 or more crypts. These findings may help to identify key targets in the early steps of colon carcinogenesis, against which drugs that would be broadly effective for chemoprevention of colon cancer could be developed.

Synthesis and conformational property of tannin-like p-tert-butylcalix[4]arene 1,3-diesters stabilized by intramolecular hydrogen bonds.

Tannin-like p-tert-butylcalix[4]arene 1,3-digallate was synthesized, and its conformational property was investigated by dynamic (1)H NMR and X-ray crystallography. It was found that the 3-OH (or 5-OH) group of the galloyl group in p-tert-butylcalix[4]arene 1,3-digallate is placed at the position where an unusual nonbonded close contact is observed between the OH group and the aromatic ring of the galloyl group facing each other. The calixarene 1,3-diesters of various hydroxybenzoic acids were also prepared, and the conformational properties of those calixarenes were compared with that of p-tert-butylcalix[4]arene 1,3-digallate. A significant contribution of the 3- and 5-OH groups in pendant groups toward the close contact was found. It was suggested that the conformation of p-tert-butylcalix[4]arene 1,3-digallate was stabilized by intramolecular hydrogen bonds including OH.O and OH-pi interactions.

Reduced Fhit expression occurs in the early stage of esophageal tumorigenesis: no correlation with p53 expression and apoptosis.

The FHIT gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene involved in multiple tumors, including esophageal carcinoma. We analyzed Fhit expression using an immunohistochemical method in invasive carcinoma, carcinoma in situ (CIS) and dysplasia, in paraffin sections of 75 esophageal squamous cell carcinomas (ESCs) to further elucidate the role of Fhit protein in esophageal carcinogenesis. In addition, we also examined whether Fhit expression correlated with p53 expression and apoptosis. Compared to adjacent normal mucosa, significant loss or reduction of Fhit expression was noted in 67 of 75 (89.3%) invasive ESCs, in 13 of 19 (68.4%) CIS lesions, and in 10 of 23 (43.5%) dysplastic lesions. There was a progressive loss or reduction of Fhit expression with progressive increases in the severity of histopathological changes (p < 0.001). However, there was no association between Fhit expression and clinicopathological findings, including tumor stage, lymph node metastasis, or overall survival. Moreover, Fhit expression was not significantly associated with p53 expression and apoptosis. These results indicate that abnormal Fhit expression is a common event in the early stage of ESC development and may occur independently of p53 expression and apoptosis mechanisms.

Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress.

Under conditions of endoplasmic reticulum (ER) stress, mammalian cells induce both translational repression and the unfolded protein response that transcriptionally activates genes encoding ER-resident molecular chaperones. To date, the only known pathway for translational repression in response to ER stress has been the phosphorylation of eIF-2alpha by the double-stranded RNA-activated protein kinase (PKR) or the transmembrane PKR-like ER kinase (PERK). Here we report another pathway in which the ER transmembrane kinase/ribonuclease IRE1beta induces translational repression through 28S ribosomal RNA cleavage in response to ER stress. The evidence suggests that both pathways are important for efficient translational repression during the ER stress response.

Synthesis of feruloyl-myo-inositols and their inhibitory effects on superoxide generation.

Ester compounds consisting of ferulic acid and myo-inositol, obtained from rice bran, were synthesized. The inhibitory effects of these feruloyl-myo-inositols on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced superoxide (O2-) generation were examined using differentiated HL-60 cells. Among the derivatives tested, only 3,4,5,6-tetra-O-acetyl-1,2-di-O-[3-(4'-acetoxy-3'-methoxyphenyl)-2-pr openoyl]-myo-inositol (3) showed a distinct inhibitory activity.

Suppressive effects of novel ferulic acid derivatives on cellular responses induced by phorbol ester, and by combined lipopolysaccharide and interferon-gamma.

A total of 23 ferulic acid (FA) derivatives were synthesized, and investigated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus (EBV) activation and superoxide (O(2)(-)) generation. Most of the derivatives showed significant EBV activation suppression or cytotoxicity at a concentration of 100 microM, with FA15 as the most potent suppressor. In both assays, FA6-FA17, bearing straight- or branched-alkyl side chains, exhibited marked suppression of O(2)(-) generation, with both FA16 and FA17 being highly active, while FA itself was virtually inactive. The activity differences seen between FA16/FA17 and FA are attributable, at least in part, to their cellular incorporating efficiencies. Further, both FA15 and FA21 attenuated the expression of inducible nitric oxide synthase and cyclooxygenase-2 proteins, while FA did not. Our results suggest that these novel FA derivatives are effective chemopreventive agents.

Synthesis, Structure, and Complexing Property of p-tert-Butylcalix

p-tert-Butylcalix[4]arene 1,3-digallate, which contains a nonbonded close contact between galloyl groups, was synthesized and its structure was determined by dynamic (1)H NMR and X-ray crystallography. The electronic spectra showed that a new absorption band of the complexes appeared at a longer wavelength region upon adding Ag(+) ion. This spectral shift was explained in terms of the interaction between the facing galloyl groups of the lower rim of the calixarene framework.

Circulating p53 antibody in patients with colorectal cancer: relation to clinicopathologic features and survival.

The presence of serum anti-p53 antibody has been reported to be associated with survival of patients with breast cancer, ovarian cancer, and hepatocellular carcinoma. To clarify prognostic significance of p53 antibody in colorectal cancer, serum p53 antibody was measured in patients with colorectal cancer. The 89 patients included 71 with colorectal cancer and 18 with colon polyp. An enzyme-linked immunosorbent assay was used to detect p53 antibodies in serum. Clinicopathological parameters such as age, sex, degree of differentiation of cancer, location of tumor, liver metastasis, stage classification, Dukes classification, CEA, CA19-9, and immunostaining of p53 and anti-p53 antibody were evaluated as prognostic factors of colorectal cancer. p53 antibody was positive in 18 of 71 (25%) with colorectal cancer, whereas it was positive in only 1 of 18 (6%) with colon polyp. The patients with p53 antibody had higher CEA and CA19-9 levels, higher positive rates of p53 protein expression in cancer cells, and higher liver metastasis rates. The p53 antibody positivity at stage classification I-IIIb/ Dukes classification A-C was significantly lower than that at stage classification IV/Dukes classification D. Overall survival in colorectal cancer patients with p53 antibody was significantly shorter than in those without p53 antibody. A Cox regression analysis showed that liver metastasis, stage classification, Dukes classification, CA19-9, and p53 antibody were significant prognostic factors in colorectal cancer. Serum anti-p53 antibody could serve as one of the prognostic factors in patients with colorectal cancer.

Elastofibroma of the sigmoid colon.

A case of elastofibroma occurring in the sigmoid colon of a 69 year-old woman is reported. The woman presented for survey of her gastrointestinal tract. Colonoscopy disclosed two polyps in the sigmoid colon, one of which was clinically considered to be recurrent adenoma. Histologically, the lesion had characteristic eosinophilic fibers and globules, termed elastofibroma fibers with hematoxylin and eosin stain. In addition, these elastinophilic materials were digested by elastase. Histological evaluation confirmed the diagnosis of elastofibroma. Our case might suggest that it is the result of long-term fibrosis after previous endoscopic resection of a sigmoid colonic adenoma.

Identification of a novel mammalian endoplasmic reticulum-resident KDEL protein using an EST database motif search.

Several endoplasmic reticulum (ER)-resident proteins contain a unique C-terminal sequence (KDEL) which is required for the retention of these proteins in the ER. By searching a mouse EST database for records containing the nucleotide sequence encoding the KDEL motif, we extracted cDNAs encoding putative novel ER-resident proteins in addition to all of the known ER proteins bearing the KDEL motif. Using the sequence information obtained by this database search, we cloned the cDNA encoding a novel KDEL motif-bearing protein, ER protein 58 (EP58), sharing no significant homology to any of the known ER-resident proteins. Subcellular localization of EP58 in the ER was confirmed by cytoimmunofluorescence studies using epitope-tagged EP58. The EP58 gene was primarily expressed in embryo, placenta, and adult heart. Neither heat shock nor ER stress as tested here was sufficient to induce expression of the EP58 gene. A putative role of the N-terminal half of EP58 in protein-protein interaction is suggested by its similarity to the filamin rod domain. Similarity of the EP58 sequence with bacterial and fungus proteins suggests a possible role for EP58 in polysaccharide biosynthesis.

Preparation of ferulic acid and its application for the synthesis of cancer chemopreventive agents.

We suggest that chemical raw materials can best be obtained from natural resources. Ferulic acid is easily prepared in large quantities from rice bran pitch, a blackish brown waste oil with high viscosity, discharged in the process of the rice bran oil production. As an application of ferulic acid, potential cancer chemopreventive agents could be synthesized using organic synthetic methods.

A novel histamine 2(H2) receptor antagonist with gastroprotective activity. II. Synthesis and pharmacological evaluation of 2-furfuryl-thio and 2-furfurylsulfinyl acetamide derivatives with heteroaromatic rings.

We recently found that N-[3-[3-(piperidinomethyl)phenoxyl]propyl]acetamide derivatives with a thioether function showed gastric anti-secretory and gastroprotective activities and that the thioether function (particularly furfurylthio or furfurylsulfinyl) was essential for gastroprotection. In the present study, a series of 2-furfurylthio and 2-furfurylsulfinyl acetamide derivatives were synthesized and evaluated for histamine H2 receptor antagonistic activity, gastric anti-secretory activity and gastroprotective action. Based on the structure of N-[3-[3-(piperidinomethyl)phenoxyl]propyl]acetamide, we designed compounds, in which the 3-(piperidinomethyl)phenoxy part is substituted with many types of heteroaromatic ring attached to the tertiary amine and the propyl group is replaced with other carbon linkages. Structure-activity relationships are discussed. 2-Furfurylsulfinyl-N-[4-[4-(piperidinomethyl)-2-pyridylox y]- (Z)-2-butenyl]acetamide was the most potent among the tested compounds and was given the code designation FRG-8813.

Clinical significance of serum P53 antibody in patients with gastric cancer.

The presence of serum p53 antibody has been reported to have prognostic significance in patients with breast and ovarian cancers. In order to clarify clinical and prognostic significance of p53 antibody in serum, we measured p53 antibody in patients with gastric cancer. Twenty-five patients with gastric cancer were examined as well as 9 patients with gastric polyp as controls. Eight of 25 patients (32%) with gastric cancer were positive for p53 antibody, while no patients with gastric polyp were positive in gastric polyp group (p < 0.05). The presence of p53 antibody was significantly associated with histology, liver metastasis and stage classification in gastric cancer (p < 0.05, respectively). Presence of liver metastasis, type of histology and presence of p53 antibody are independent prognostic factors (p < 0.05, respectively). The overall survival in patients with p53 antibody was significantly shorter survival than for those without antibody (p < 0.05%). These data suggest that p53 antibody serves as one of the prognostic factors in gastric cancer.

Microvascular change of the anterior eye segment after tenotomy in the rabbit.

BACKGROUND: The microvascular changes secondary to anterior segment ischemia following tenotomy of the extraocular muscles have not been studied in the rabbit. METHODS: Using scanning electron microscopy of methyl-methacrylate ocular microvascular luminal castings, the anterior eye segment vasculature after tenotomy was documented and compared to that after occlusion of the bilateral long posterior ciliary arteries and that in the eyes that were not subjected to any surgical intervention. RESULTS: Five days and 1 week after the surgical intervention with tenotomy, microvascular change secondary to the anterior segment ischemia was not apparent, but 2 weeks after the tenotomy subtle evidence of ischemia such as new vessels in the iris was observed. Seven weeks after tenotomy, marked microvascular change was observed where corneal new vessels arose from the superior perilimbal arteries. In contrast, we found prominent microvascular changes 2 weeks after the occlusion of the long posterior ciliary arteries. CONCLUSIONS: Tenotomy of the rabbit eye causes microvascular change similar to that in occlusion of the long posterior ciliary arteries. This result suggests that the anterior ciliary artery of the rabbit contributes blood flow to the anterior eye segment and also has a stronger connection with the long posterior ciliary artery than previously reported.